Comparison between catheter ablation versus permanent pacemaker implantation as an initial treatment for tachycardia-bradycardia syndrome patients: a prospective, randomized trial.

BACKGROUND: Clinical outcomes after catheter ablation (CA) or pacemaker (PM) implantation for the tachycardia-bradycardia syndrome (TBS) has not been evaluated adequately. We tried to compare the efficacy and safety outcomes of CA and PM implantation as an initial treatment option for TBS in paroxysmal atrial fibrillation (AF) patients. METHODS: Sixty-eight patients with paroxysmal AF and TBS (mean 63.7 years, 63.2% male) were randomized, and received CA (n = 35) or PM (n = 33) as initial treatments. The primary outcomes were unexpected emergency room visits or hospitalizations attributed to cardiovascular causes. RESULTS: In the intention-to-treatment analysis, the rates of primary outcomes were not significantly different between the two groups at the 2-year follow-up (19.8% vs. 25.9%; hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.25-2.20, P = 0.584), irrespective of whether the results were adjusted for age (HR 1.12, 95% CI 0.34-3.64, P = 0.852). The 2-year rate of recurrent AF was significantly lower in the CA group compared to the PM group (33.9% vs. 56.8%, P = 0.038). Four patients (11.4%) in the CA group finally received PMs after CA owing to recurrent syncope episodes. The rate of major or minor procedure related complications was not significantly different between the two groups. CONCLUSION: CA had a similar efficacy and safety profile with that of PM and a higher sinus rhythm maintenance rate. CA could be considered as a preferable initial treatment option over PM implantation in patients with paroxysmal AF and TBS. TRIAL REGISTRATION: KCT0000155.

Ivabradine restores tonic cardiovascular autonomic control and reduces tachycardia, hypertension and left ventricular inflammation in post-weaning protein malnourished rats.

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. AIM: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. MAIN METHODS: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. KEY FINDINGS: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. SIGNIFICANCE: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.

Clinical Characterization of Arrhythmia-Induced Cardiomyopathy in Patients With Tachyarrhythmia and Idiopathic Heart Failure.

BACKGROUND: Arrhythmia-induced cardiomyopathy (AIC) is a known entity, but prospective evidence for its characterization is limited. OBJECTIVES: This study aimed to: 1) determine the relative frequency of the pure form of AIC in the clinically relevant cohort of patients with newly diagnosed, otherwise unexplained left ventricular systolic dysfunction (LVSD) and tachyarrhythmia; 2) assess the time to recovery from LVSD; and 3) identify parameters for an early diagnosis of AIC. METHODS: Patients were prospectively included, underwent effective rhythm restoration, and were followed-up at 2, 4, and 6 months to evaluate clinical characteristics, biomarkers, and cardiac imaging including cardiac magnetic resonance imaging. Patients with recurred arrhythmia were excluded from analysis. RESULTS: 41 of 50 patients were diagnosed with AIC 6 months after rhythm restoration. Left ventricular (LV) ejection fraction increased 2 months after rhythm restoration from 35.4% ± 8.2% to 52.7% ± 8.0% in AIC patients vs 37.0% ± 9.5% to 43.3% ± 7.0% in non-AIC patients. From month 2 to 6, LV ejection fraction continued to increase in AIC patients (57.2% ± 6.1%; P < 0.001) but remained stable in non-AIC patients (44.0% ± 7.8%; P = 0.628). Multivariable logistic regression analysis revealed that lower LV end-diastolic diameter at baseline could be used for early diagnosis of AIC, whereas biomarkers and other morphological or functional parameters, including late LV gadolinium enhancement, did not show suitability for early diagnosis. CONCLUSIONS: We observed a high prevalence of AIC in patients with otherwise unexplained LVSD and concomitant tachyarrhythmia, suggesting that this condition may be underdiagnosed in clinical practice. Most patients recovered fast, within months, from LVSD. A low initial LV end-diastolic diameter may constitute an early marker for diagnosis of AIC.

Adeno-associated virus-mediated gene therapy for cardiac tachyarrhythmia: A systematic review and meta-analysis.

Cardiac tachyarrhythmia presents a significant health care challenge, causing notable morbidity and mortality. Conventional treatments have limitations and potential risks, resulting in an elevated disease burden. Adeno-associated virus (AAV)-mediated gene therapy holds promise as a potential future treatment option. Therefore, we aimed to provide a measured overview of the latest developments in this rapidly growing field. PubMed and Embase databases were searched up to January 2024. Studies that employed AAV as a vector for delivery of therapeutic agents to treat cardiac tachyarrhythmia were included. Of the 26 studies included, 20 published in the last 5 years. There were 22 novel molecular targets identified. More than 80% of the included studies employed small-animal models or used AAV9. In atrial fibrillation preclinical studies, AAV-mediated gene therapy reduced atrial fibrillation inducibility by 81% (odds ratio, 0.19 [0.08-0.45]; P < .01). Similarly, for acquired and inherited ventricular arrhythmia, animal models receiving gene therapy had less inducible ventricular arrhythmia (odds ratio, 0.06 [0.03-0.11]; P < .01). This review highlights the rapid progress of AAV-mediated gene therapy for cardiac tachyarrhythmia. Although these investigations are currently in the early stages of clinical application, they present promising prospects for gene therapy. (PROSPERO registry: CRD42023479448).

Cardiogenic control of affective behavioural state.

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1-3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3-8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour.

Cardiorespiratory anomalies and increased brainstem microglia in a rat model of neonatal opioid withdrawal syndrome.

Infants born with neonatal opioid withdrawal syndrome (NOWS) can display abnormal cardiorespiratory patterns including tachypnea, tachycardia, and impaired ventilatory responses to hypoxia (HVR) and hypercapnia (HCVR). Chronic morphine exposure is associated with increased midbrain microglial expression. Using a rat model of pre- and post-natal morphine exposure, we assessed cardiorespiratory features of NOWS (resting tachycardia and tachypnea) including the attenuated HVR and HCVR and whether they are associated with increased brainstem microglia expression. Pregnant rats (dams) received twice-daily subcutaneous injections of morphine (5 mg/kg) during the third (last) week of pregnancy to simulate 3rd trimester in utero opioid exposure. Offspring then received once-daily subcutaneous injections of morphine (0.5 mg/kg) until postnatal (P) day P10 days of age to simulate postnatal morphine therapy. Cardiorespiratory responses were assessed 24 h later (P11 days) following spontaneous withdrawal. Compared to saline-treated pups, morphine-exposed offspring exhibited tachycardia and tachypnea as well as an attenuated HVR and HCVR. Microglial cell counts were increased in the nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus (DMNV) and nucleus ambiguous (NAamb), but not the retrapezoid nucleus (RTN) or the non-cardiorespriatory region, the cuneate nucleus (CN). These data suggest that the cardiorespiratory features and autonomic dysregulation in NOWS infants may be associated with altered microglial function in specific brainstem cardiorespiratory control regions.

A Simple Emergency Department-Based Score Predicts Complex Hospitalization in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Thirty percent of inflammatory bowel disease (IBD) patients hospitalized with flare require salvage therapy or surgery. Additionally, 40% experience length of stay (LOS) > 7 days. No emergency department (ED)-based indices exist to predict these adverse outcomes at admission for IBD flare. We examined whether clinical, laboratory, and endoscopic markers at presentation predicted prolonged LOS, inpatient colectomy, or salvage therapy in IBD patients admitted with flare. METHODS: Patients with ulcerative colitis (UC) or colonic involvement of Crohn's disease (CD) hospitalized with flare and tested for Clostridioides difficile infection (CDI) between 2010 and 2020 at two urban academic centers were studied. The primary outcome was complex hospitalization, defined as: LOS > 7 days, inpatient colectomy, or inpatient infliximab or cyclosporine. A nested k-fold cross-validation identified predictive factors of complex hospitalization. RESULTS: Of 164 IBD admissions, 34% (56) were complex. Predictive factors included: tachycardia in ED triage (odds ratio [OR] 3.35; confidence interval [CI] 1.79-4.91), hypotension in ED triage (3.45; 1.79-5.11), hypoalbuminemia at presentation (2.54; 1.15-3.93), CDI (2.62; 1.02-4.22), and endoscopic colitis (4.75; 1.75-5.15). An ED presentation score utilizing tachycardia and hypoalbuminemia predicted complex hospitalization (area under curve 0.744; CI 0.671-0.816). Forty-four of 48 (91.7%) patients with a presentation score of 0 (heart rate < 99 and albumin ≥ 3.4 g/dL) had noncomplex hospitalization. CONCLUSIONS: Over 90% of IBD patients hospitalized with flare with an ED presentation score of 0 did not require salvage therapy, inpatient colectomy, or experience prolonged LOS. A simple ED-based score may provide prognosis at a juncture of uncertainty in patient care.

Wide complex tachycardia in a patient with non-ischemic cardiomyopathy: What is the diagnosis?

A 55-year-old male presented with acute heart failure and incessant wide complex tachycardia resembling an outflow tract ventricular tachycardia. Meticulous analysis of the electrocardiograms established the diagnosis of pre-excitation with prolonged atrio-ventricular (A-V) conduction over a decrementally conducting accessory A-V pathway. "Linking" between the accessory A-V pathway and normal A-V conduction system resulted in sustained maximal pre-excitation as well as periodic transition to normal A-V conduction without appreciable change in heart rate. Successful radiofrequency ablation of this unusual accessory A-V pathway was performed at the aortic-mitral junction. This ameliorated the mechanical dysynchrony, allowed discontinuation of hemodynamic/inotropic support, and resulted in sustained symptomatic improvement.

A Case of Heart Palpitations and a Rapid Pulse.

Editor's note: This article is one in a series on electrocardiogram (ECG) interpretation. Nurses in all settings should know the basics, as medications and physiological changes can cause cardiac arrhythmias. Each article will start with a brief case scenario and an ECG strip and then take you step by step through analyzing the heart rhythm. To see all the articles in the series, go to http://links.lww.com/AJN/A207.

Macro-reentrant atrial tachycardia after tricuspid or mitral valve surgery: is there difference in electrophysiological characteristics and effectiveness of catheter ablation?

BACKGROUND: Macro-reentrant atrial tachycardias (MATs) are a common complication after cardiac valve surgery. The MAT types and the effectiveness of MAT ablation might differ after different valve surgery. Data comparing the electrophysiological characteristics and the ablation results of MAT post-tricuspid or mitral valve surgery are limited. METHODS: Forty-eight patients (29 males, age 56.1 ± 13.3 years) with MAT after valve surgery were assigned to tricuspid valve (TV) group (n = 18) and mitral valve (MV) group (n = 30). MATs were mapped and ablated guided by a three-dimensional navigation system. The one-year clinical effectiveness was compared in two groups. RESULTS: Nineteen MATs were documented in TV group, including 16 cavo-tricuspid isthmus (CTI)-dependent AFL and 3 other MATs at right atrial (RA) free wall, RA septum and left atrial (LA) roof. Thirty-nine MATs were identified in MV group, including15 CTI-dependent AFL, 8 RA free wall scar-related, 2 RA septum scar-related, 8 peri-mitral flutter, 3 LA roof-dependent, 2 LA anterior scar-related, and 1 right pulmonary vein-related MAT. Compared with TV group, MV group had significantly lower prevalence of CTI-dependent AFL (38.5% vs. 84.2%), higher prevalence of left atrial MAT (35.9 vs.5.3%) and higher proportion of patients with left atrial MAT (40 vs. 5.6%), P = 0.02, 0.01 and 0.01, respectively. The acute success rate of MAT ablation (100 vs. 93.3%) and the one-year freedom from atrial tachy-arrhythmias (72.2 vs. 76.5%) was comparable in TV and MV group. No predictor for recurrence was identified. CONCLUSION: Although the types of MATs differed significantly in patients with prior TV or MV surgery, the acute and mid-term effectiveness of MAT ablation was comparable in two groups. TRIAL REGISTRATION: This study was registered as a part of EARLY-MYO-AF clinical trial at the website ClinicalTrials. gov (NCT04512222).

Tachycardia and hypertension enhance tracer efflux from the spinal cord.

BACKGROUND: Disruption of cerebrospinal fluid (CSF)/interstitial fluid (ISF) exchange in the spinal cord is likely to contribute to central nervous system (CNS) diseases that involve abnormal fluid accumulation, including spinal cord oedema and syringomyelia. However, the physiological factors that govern fluid transport in the spinal cord are poorly understood. The aims of this study were to determine the effects of cardiac pulsations and respiration on tracer signal increase, indicative of molecular movement following infusion into the spinal cord grey or white matter. METHODS: In Sprague Dawley rats, physiological parameters were manipulated such that the effects of spontaneous breathing (generating alternating positive and negative intrathoracic pressures), mechanical ventilation (positive intrathoracic pressure only), tachycardia (heart atrial pacing), as well as hypertension (pharmacologically induced) were separately studied. Since fluid outflow from the spinal cord cannot be directly measured, we assessed the molecular movement of fluorescent ovalbumin (AFO-647), visualised by an increase in tracer signal, following injection into the cervicothoracic spinal grey or white matter. RESULTS: Tachycardia and hypertension increased AFO-647 tracer efflux, while the concomitant negative and positive intrathoracic pressures generated during spontaneous breathing did not when compared to the positive-pressure ventilated controls. Following AFO-647 tracer injection into the spinal grey matter, increasing blood pressure and heart rate resulted in increased tracer movement away from the injection site compared to the hypotensive, bradycardic animals (hypertension: p = 0.05, tachycardia: p < 0.0001). Similarly, hypertension and tachycardia produced greater movement of AFO-647 tracer longitudinally along the spinal cord following injection into the spinal white matter (p < 0.0001 and p = 0.002, respectively). Tracer efflux was strongly associated with all blood vessel types. CONCLUSIONS: Arterial pulsations have profound effects on spinal cord interstitial fluid homeostasis, generating greater tracer efflux than intrathoracic pressure changes that occur over the respiratory cycle, demonstrated by increased craniocaudal CSF tracer movement in the spinal cord parenchyma.

Atrial high-rate episodes predict major adverse cardio/cerebrovascular events in patients with cardiac implantable electrical devices.

Patients with atrial high-rate episodes (AHRE) have a high risk of neurologic events, although the causal role and optimal cutoff threshold of AHRE for major adverse cardio/cerebrovascular events (MACCE) are unknown. This study aimed to identify independent factors for AHRE and subsequent atrial fibrillation (AF) after documented AHRE. We enrolled 470 consecutive patients undergoing cardiac implantable electrical device (CIED) implantations. The primary endpoint was subsequent MACCE after AHRE ≥ 6 min, 6 h, and 24 h. AHRE was defined as > 175 beats per minute (bpm) (Medtronic®) or > 200 bpm (Biotronik®) lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine variables associated with independent risk of MACCE. The patients' median age was 76 year, and 126 patients (26.8%) developed AHRE ≥ 6 min, 63 (13.4%) ≥ 6 h, and 39 (8.3%) ≥ 24 h. During follow-up (median: 29 months), 142 MACCE occurred in 123 patients. Optimal AHRE cutoff value was 6 min, with highest Youden index for MACCE. AHRE ≥ 6 min ~ 24 h was independently associated with MACCE and predicted subsequent AF. Male gender, lower body mass index, or BMI, and left atrial diameter were independently associated with AHRE ≥ 6 min ~ 24 h. Patients with CIEDs who develop AHRE ≥ 6 min have an independently increased risk of MACCE. Comprehensive assessment of patients with CIEDs is warranted.

Lateral hypothalamus involvement in control of stress response by bed nucleus of the stria terminalis endocannabinoid neurotransmission in male rats.

The endocannabinoid neurotransmission acting via local CB1 receptor in the bed nucleus of the stria terminalis (BNST) has been implicated in behavioral and physiological responses to emotional stress. However, the neural network related to this control is poorly understood. In this sense, the lateral hypothalamus (LH) is involved in stress responses, and BNST GABAergic neurons densely innervate this hypothalamic nucleus. However, a role of BNST projections to the LH in physiological responses to stress is unknown. Therefore, using male rats, we investigated the role of LH GABAergic neurotransmission in the regulation of cardiovascular responses to stress by CB1 receptors within the BNST. We observed that microinjection of the selective CB1 receptor antagonist AM251 into the BNST decreased the number of Fos-immunoreactive cells within the LH of rats submitted to acute restraint stress. Treatment of the BNST with AM251 also enhanced restraint-evoked tachycardia. Nevertheless, arterial pressure increase and sympathetically-mediated cutaneous vasoconstriction to restraint was not affected by CB1 receptor antagonism within the BNST. The effect of AM251 in the BNST on restraint-evoked tachycardia was abolished in animals pretreated with the selective GABAA receptor antagonist SR95531 in the LH. These results indicate that regulation of cardiovascular responses to stress by CB1 receptors in the BNST is mediated by GABAergic neurotransmission in the LH. Present data also provide evidence of the BNST endocannabinoid neurotransmission as a mechanism involved in LH neuronal activation during stressful events.

Interatrial septal tachycardias following atrial fibrillation ablation or cardiac surgery: Electrophysiological features and ablation outcomes.

BACKGROUND: Interatrial septal tachycardias (IAS-ATs) following atrial fibrillation (AF) ablation or cardiac surgery are rare, and their management is challenging. OBJECTIVE: The purpose of this study was to investigate the electrophysiological features and outcomes associated with catheter ablation of IAS-AT. METHODS: We screened 338 patients undergoing catheter ablation of ATs following AF ablation or cardiac surgery. Diagnosis of IAS-AT was based on activation mapping and analysis of response to atrial overdrive pacing. RESULTS: Twenty-nine patients (9%) had IAS-AT (cycle length [CL] 311 ± 104 ms); 16 (55%) had prior AF ablation procedures (median 3; range 1-5), 3 (10%) had prior surgical maze, and 12 (41%) had prior cardiac surgery (including atrial septal defect surgical repair in 5 and left atrial myxoma resection in 1). IAS substrate abnormalities were documented in all patients. Activation mapping always demonstrated a diffuse early IAS breakout with centrifugal biatrial activation, and atrial overdrive pacing showed a good postpacing interval (equal or within 25 ms of the AT CL) only at 1 or 2 anatomically opposite IAS sites in all cases. Ablation was acutely successful in 27 patients (93%) (from only the right IAS in 2, only the left IAS in 9, both IAS sides with sequential ablation in 13, and both IAS sides with bipolar ablation in 3). After median follow-up of 15 (6-52) months, 17 patients (59%) remained free from recurrent arrhythmias. CONCLUSION: IAS-ATs are rare and typically occur in patients with evidence of IAS substrate abnormalities and prior cardiac surgery. Catheter ablation can be challenging and may require sequential unipolar ablation or bipolar ablation.

Discordant responses to his refractory premature ventricular beats (PVBs) during a regular narrow QRS tachycardia. What is the mechanism.

A 32-year-old lady was evaluated for recurrent episodes of palpitation. During one of the palpitation episodes a regular narrow QRS tachycardia was documented, and it got terminated with the administration of IV adenosine. The baseline 12 lead electrocardiogram (ECG) did not show any manifest preexcitation. There was no evidence of structural heart disease by echocardiogram. Patient underwent an electrophysiology (EP) study after informed consent. Quadripolar catheters were placed at the His region and right ventricular (RV) apex. A decapolar catheter was placed in the coronary sinus (CS) with CS 9, 10 dipoles at CS OS region and CS 1, 2 dipoles at CS distal region. A mapping & ablation catheter was positioned at right atrial (RA) appendage. Baseline atrial and ventricular pacing protocols could not be performed as both atrial and ventricular pacing were easily inducing a regular narrow QRS tachycardia. His refractory premature ventricular beats [PVBs] were delivered from RVRV apex and left ventricular [LV] free wall. Discordant responses were obtained. What is the mechanism?